Pediatric Concerns
Amit Golding, MD, PhD, medical officer with the FDA Division of Rheumatology and Transplant Medicine, said the “extrapolation of efficacy” concept has been growing in importance in pediatric rheumatology.
“It has been the basis for a number of recent pediatric approvals in rheumatology,” he said.
Approvals follow a continuum, according to this philosophy. When indications in pediatrics are considered essentially distinct, without a matching adult counterpart, well-controlled clinical studies are required. On the other end of the spectrum are pediatric conditions that are considered highly similar to the adult condition. In these cases, approval might only require simple pharmacokinetic safety studies evaluating a single dose level that matches adult exposures, Dr. Golding said.
For conditions with partial similarities, approval may rely on controlled or descriptive efficacy studies, using biomarkers, if available and appropriate, as a bridge from adults to pediatrics and using statistical inferences.
Belimumab, approved for pediatric lupus nephritis in July 2022—the first for this population of patients—is an example of how the extrapolation approach is used. The components of this approval, Dr. Golding said, were similarity of the disease between adults and pediatric patients, a pharmacokinetic bridge study, extrapolation of efficacy in pediatric patients from that in adult patients with lupus nephritis, and a justification that safety data on patients with systemic lupus erythematosus was relevant to this group of patients.
FDA officials were asked about the value of enrolling younger patients in trials.
Nikolay Nikolov, MD, director of the Division of Rheumatology and Transplant Medicine, encouraged the enrollment of adolescents, when possible. This, he said, can “inform extrapolation to smaller age groups.”
“As long as there is data to support the prospect of direct benefits, which usually comes from a phase 2 clinical study data or from earlier development of the product in adults, that’s sort of a fundamental requirement for us to allow pediatric patients to be studied,” he said.
“We’ve heard from the community that this is challenging to coordinate, and to do that practically, but we have seen proposals and programs including adolescents successfully.”
Thomas R. Collins is a freelance medical writer based in Florida.
